Podocyte Number in Children and Adults: Associations with Glomerular Size and Numbers of Other Glomerular Resident Cells

Victor G. Puelles, Rebecca N. Douglas-Denton, Luise A. Cullen-McEwen, Jinhua Li, Michael D. Hughson, Wendy E. Hoy, Peter G. Kerr, John F. Bertram

Increases in glomerular size occur with normal body growth and in many pathologic conditions. In this study, we determined associations between glomerular size and numbers of glomerular resident cells, with a particular focus on podocytes. Kidneys from 16 male Caucasian-Americans without overt renal disease, including 4 children (≤3 years old) to define baseline values of early life and 12 adults (≥18 years old), were collected at autopsy in Jackson, Mississippi. We used a combination of immunohistochemistry, confocal microscopy, and design-based stereology to estimate individual glomerular volume (IGV) and numbers of podocytes, nonepithelial cells (NECs; tuft cells other than podocytes), and parietal epithelial cells (PECs). Podocyte density was calculated. Data are reported as medians and interquartile ranges (IQRs). Glomeruli from children were small and contained 452 podocytes (IQR=335-502), 389 NECs (IQR=265-498), and 146 PECs (IQR=111-206). Adult glomeruli contained significantly more cells than glomeruli from children, including 558 podocytes (IQR=431-746; P<0.01), 1383 NECs (IQR=998-2042; P<0.001), and 367 PECs (IQR=309-673; P<0.001). However, large adult glomeruli showed markedly lower podocyte density (183 podocytes per 10(6) µm(3)) than small glomeruli from adults and children (932 podocytes per 10(6) µm(3); P<0.001). In conclusion, large adult glomeruli contained more podocytes than small glomeruli from children and adults, raising questions about the origin of these podocytes. The increased number of podocytes in large glomeruli does not match the increase in glomerular size observed in adults, resulting in relative podocyte depletion. This may render hypertrophic glomeruli susceptible to pathology.